PI3K/Akt signaling pathway is involved in the pathogenesis of ulcerative colitis

Abstract

The PI3K/Akt signal transduction pathway is involved in the regulation and release of pro-inflammatory cytokines such as TNF-α and plays an important role in the development and progression of UC.

A preferential p110α/γ PI3K inhibitor attenuates experimental inflammation by suppressing the production of proinflammatory mediators in a NF-κB-dependent manner

“…6). These observations with a preferential p110␣/␥ PI3K inhibitor complement earlier studies showing that 1) intravenous administration of small interfering RNA directed against the p85␣ subunit of PI3K markedly attenuates inflammatory changes associated with DSS-induced colitis (49); 2) intrarectal administration of small interfering RNA directed against the p85␣ subunit of PI3K significantly increases the survival of mice treated with DSS (29); and 3) wortmannin (an earliest broad-acting PI3K inhibitor) suppresses DSS-induced colitis (28). To the best of our knowledge, this is the first report of a preferential PI3K-␣/␥ inhibitor that not only blocks induced NF-B activation and consequent production/function of proinflammatory cytokines in human cells, but also attenuates experimental colitis when administered orally in a therapeutic regimen.…”

Dietary Kaempferol Suppresses Inflammation of Dextran Sulfate Sodium-Induced Colitis in Mice

“…Recent studies have demonstrated that the imbalance of pro-inflammatory cytokines and anti-inflammatory cytokines are related to the pathogenic mechanisms of UC [24]. Activation of the PI3K/Akt and NF-jB signal transduction pathway facilitate the expression and secretion of pro-inflammatory cytokines which create imbalanced cytokine profiles [25]. In this study, kaempferol diets effectively down-regulated the colonic mRNA expression level of the major pro-inflammatory cytokines, e.g., TNF-a, IL-1b, and IL-6, which indicate that kaempferol plays a role in the cytokines production.…”

Comparative Protective Effect of Hawthorn Berry Hydroalcoholic Extract, Atorvastatin, and Mesalamine on Experimentally Induced Colitis in Rats

“…The abnormal release of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-a) and prostaglandin D2 are important mediators in the pathogenesis of UC. 4,5 In general, the medical treatment of UC starts with 5-aminosalicylic acid as the baseline medication, followed by steroids and immunomodulators. Moreover, to intensify the treatment, infliximab, calcineurin inhibitors (cyclosporine A and tacrolimus), or surgery may be considered as rescue therapy.…”